Feb 11, 2020: Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Japan  announced that the U.S. FDA has accepted for Priority Review its NDA for oral C-DEC (cedazuridine and decitabine) as a treatment for adult patients with previously untreated intermediate- and high-risk MDS including CMML.
The NDA submission is based on the data from the ASCERTAIN phase 3 study which evaluated the 5-day decitabine exposure equivalence of oral C-DEC and IV decitabine.
The FDA grants Priority Review to the applications for drugs that, if approved, would provide significant improvements in the safety and efficacy of the treatment, diagnosis or prevention of serious conditions. The Priority Review designation means the FDA’s goal is to take action on an NDA application within six months. Oral C-DEC (investigational compound) not currently approved in any country.
 About C-DEC (Cedazuridine 100 mg and Decitabine 35 mg) Fixed-Dose CombinationC-DEC is a novel, orally administered fixed dose combination of the cedazuridine, an inhibitor of cytidine deaminase with the anti-cancer DNA hypomethylating agent, decitabine.
It inhibit cytidine deaminase in the gut and the liver, C-DEC is designed to permit for oral delivery of the approved DNA hypomethylating agent, decitabine, at exposures which follow exposures achieved with the approved intravenous form of the decitabine administered over 5 days.
C-DEC has been evaluated in the phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in the patients with MDS and CMML see https://www.clinicaltrials.gov NCT02103478) and also pivotal phase 3 study (ASCERTAIN)see https://www.clinicaltrials.gov NCT03306264) conducted at investigator sites in the US and Canada and designed in order to confirm the results from the phase 1/2 study.
The phase 3 study is now being comprehensive to include patients with acute myeloid leukemia (AML) unsuitable to receive intensive induction chemotherapy.
Astex announced that C-DEC had received orphan drug designation in September 2019 for the treatment of MDS and CMML from the U.S. FDA. The concept of using cedazuridine is to block the action of cytidine deaminase is also being evaluated in the low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see https://www.clinicaltrials.gov NCT03502668).
About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML): Myelodysplastic syndromes are a heterogeneous group of the hematopoietic stem cell disorders characterized by the dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias distressing one or more of the three lineages. U.S. incidence of the MDS is estimated to be 10,000 cases per year, even though the condition is thought to be under-diagnosed.
https://astx.com/astex-pharmaceuticals-announces-u-s-food-and-drug-administration-fda-acceptance-for-review-of-an-nda-for-the-combination-oral-hypomethylating-agent-cedazuridine-and-decitabine-astx727-or-oral-c-de/
